Silicon (Si) was reported to have an essential role in several organisms such as diatoms, Si accumulating plants, birds, and mammals. The formation of connective tissue components and other more specialized tissues such as bone and cartilage were shown to be dependent on the Si status. Dietary Si deficiency causes bone deformation, a thinner cortex, and a less calcified bone matrix (Carlisle, 1989, Silicon in: Handbook of Nutritionally Essential Mineral Elements, ed. B. L. Dell and R. A. Sunde, Marcel Dekker Inc., New York, pp. 603-618). Silicon deprivation in rats results in an altered bone mineral composition and decreased activity of bone specific phosphatase enzymes (Seaborn et al., 1994, J Trace Elem Exp Med, 7, 11). Therapeutic applications of silicon compounds were reported both in preclinical and clinical studies for a variety of diseases such as osteoporosis, atherosclerosis, neurodegenerative disorders, hypertension, aged skin, fragile hair and brittle nails, fungal infections, immunodeficiency, and connective tissue related diseases in general.
The bioavailability of silicon largely depends on its chemical form. Solid dietary silicon compounds have a low solubility and are poorly absorbed in the gastro-intestinal tract. Soluble silicon compounds found in beverages such as water and beer are readily absorbed and regarded as bioavailable sources of silicon. Orthosilicic acid which is the water soluble silicon compound present in these beverages is only stable at dilute concentrations. Concentrated complexes of orthosilicic acid were described with stabilizing agents such quaternary ammonium compounds and amino acids (“Stabilized orthosilicic acid comprising preparation and biological preparation”, U.S. Pat. No. 5,922,360 and EP 0473922B1). These stabilized forms of orthosilicic acid were found to have a very high bioavailability compared to other silicon compounds in both animals and humans when administered as a liquid concentrate (Calomme et al., 1998, Comparative bioavailability study of silicon supplements in healthy subjects, Journal of Parenteral and Enteral Nutrition, 22, S12 and Van Dyck et al., 1999, Bioavailability of silicon from foods and food supplements, Fresenius Journal of Analytical Chemistry, 363, 541-544). A solid galenic from is preferred compared to liquid formulations when considering important issues such as dosing accuracy and compliance.
Several experiments were made in order to formulate a bioavailable, solid galenic formulation of silicic acid stabilized with quaternary ammonium compounds such as choline chloride, or an amino acid source. It is very difficult to make such a preparation since orthosilicic acid rapidly converts into non-bioavailable gels and precipitates. In fact, the addition of solid or semi-solid excipients without the addition of a non-toxic solvent agent result in polymerization or gel formation of orthosilicic acid into macromolecules, thereby decreasing the bioavailability of the final preparation. Direct filling of gelatine or methylcellulose capsules with a liquid matrix of choline stabilized silicic acid results in deformation and leaking of the capsule when incubated in stability tests. Stabilizing agents for orthosilicic acid such as choline chloride are extremely hygroscopic and attract water from the surrounding capsule which finally results in a deformed capsule.